Cancer is now the second leading cause of death in the United States. In 1995, cancer accounted for 23.3% of all deaths in the United States. See, e.g., U.S. Dept. of Health and Human Services, National Center for Health Statistics, Health United States 1996-97 and Injury Chartbook 117 (1997).
Cancer is now primarily treated with one or a combination of three types of therapies: surgery; radiation; and chemotherapy. Surgery involves the bulk removal of diseased tissue. While surgery is sometimes effective in removing tumors located at certain sites, for example, in the breast, colon, and skin, it cannot be used in the treatment of tumors located in other areas, such as the backbone, nor in the treatment of disseminated neoplastic conditions such as leukemia. Radiation therapy involves the exposure of living tissue to ionizing radiation causing death or damage to the exposed cells. Side effects from radiation therapy may be acute and temporary, while others may be irreversible. Chemotherapy involves the disruption of cell replication, cell metabolism, or cell invasion, motility and metastasis. It is used most often in the treatment of breast, lung, and testicular cancer as well as hematologic malignancies such as leukemia and myeloma. One of the main causes of failure in this treatment of cancer is the development of drug resistance by the cancer cells, a serious problem that may lead to recurrence of disease or even death.
In one example, new treatments for breast cancer are being developed based on the understanding that the progression of breast cancer requires resistance to cell death; however, the mechanisms by which breast cancer cells acquire this attribute is not well understood. One way in which breast cancer cells are thought to accomplish this resistance to cell death is to activate Akt. Activated Akt can act through multiple pathways to promote resistance to cell death and is therefore considered to be a regulator of cancer cell survival. While the molecular mechanisms by which Akt is activated are not well understood, recent research had determined that an oral HIV protease inhibitor drug, ritonavir, FDA approved to treat AIDS, exhibits activity against breast cancer in a mouse model of mammary cancer and blocks Akt activation (see, e.g., U.S. Publication No. 2007/0009593, incorporated by reference herein). Ritonavir is one example of an emerging approach to the treatment of cancer.